A groundbreaking study has identified an inherited gene mutation that significantly increases the risk of prostate cancer in families with a history of the disease. The research, led by Vanderbilt University Medical Center and published in JCO Precision Oncology, reveals that a mutated form of the WNT9B gene, which plays a key role in embryonic prostate development, elevates the risk of developing prostate cancer in adulthood.
This discovery was confirmed across five independent study populations, representing approximately half a million patients from the US and Europe. The study found that men with this mutated gene faced a prostate cancer risk ranging from two to 12 times higher than those without the mutation, according to Jeffrey Smith, MD, PhD, associate professor of Medicine in the Division of Genetic Medicine and the study’s lead author.
“While many high-risk genes have been identified for other cancers, particularly breast cancer, relatively few have been established for prostate cancer,” Smith explained. “The inherited risk of prostate cancer is about twice that of breast cancer, but the genetic complexity is far greater, which has made global studies much more challenging.”
A pathogenic gene mutation is a change in a gene’s DNA sequence that can increase the likelihood of developing diseases like cancer. Such mutations can be inherited from a parent or acquired during a person’s lifetime. The newly discovered WNT9B mutation adds to the list of known high-risk prostate cancer genes, including HOXB13, BRCA2, and the 8q24 locus.
“The risk associated with a pathogenic WNT9B mutation is comparable to the risk associated with known breast cancer mutations, which are routinely tested in breast cancer care,” said Smith. “Understanding inherited mutations like WNT9B can guide treatment choices and help families make more informed decisions about their health.”
Looking ahead, Smith emphasized that future research will explore whether inherited or acquired mutations in the WNT9B gene could influence clinical outcomes, further refining approaches to personalized, precision care for prostate cancer patients.
This discovery represents an important step in understanding the genetic underpinnings of prostate cancer, offering new avenues for diagnosis, treatment, and prevention for those at higher genetic risk.
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